A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.

Multiple myeloma (MM) is characterized by complex genetic abnormalities whose complexity signifies varying degree of chromosomal instability (CIN). In this study, we introduced a novel CIN measure, chromosome instability genome event count (CINGEC), which considered both copy number aberrations and...

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Autores principales:	Tae-Hoon Chung, George Mulligan, Rafael Fonseca, Wee Joo Chng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f85a0564af5e41f999abd3cb5d8d4469
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spelling	oai:doaj.org-article:f85a0564af5e41f999abd3cb5d8d44692021-11-18T07:40:49ZA novel measure of chromosome instability can account for prognostic difference in multiple myeloma.1932-620310.1371/journal.pone.0066361https://doaj.org/article/f85a0564af5e41f999abd3cb5d8d44692013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23840451/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple myeloma (MM) is characterized by complex genetic abnormalities whose complexity signifies varying degree of chromosomal instability (CIN). In this study, we introduced a novel CIN measure, chromosome instability genome event count (CINGEC), which considered both copy number aberrations and interstitial breakpoints from high-resolution genome-wide assays. When assessed in two aCGH MM datasets, higher CINGEC was associated with poor survival. We then derived a CINGEC-associated gene expression profile (GEP) signature, CINGECS, using a dataset that has both aCGH and GEP. Genes in CINGECS were mainly involved in DNA damage responses besides in aneuploidy and other generic oncogenic processes contrary to other CIN associated GEP signatures. Finally, we confirmed its survival association in three GEP datasets that encompassed newly diagnosed patients treated with transplant-based protocol with or without novel agents for induction as well as relapsed patients treated with bortezomib. Furthermore, CINGECS was independent of many GEP-based prognostic signatures. In conclusion, our novel CIN measure has definite biological and clinical significance in myeloma.Tae-Hoon ChungGeorge MulliganRafael FonsecaWee Joo ChngPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66361 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tae-Hoon Chung George Mulligan Rafael Fonseca Wee Joo Chng A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
description	Multiple myeloma (MM) is characterized by complex genetic abnormalities whose complexity signifies varying degree of chromosomal instability (CIN). In this study, we introduced a novel CIN measure, chromosome instability genome event count (CINGEC), which considered both copy number aberrations and interstitial breakpoints from high-resolution genome-wide assays. When assessed in two aCGH MM datasets, higher CINGEC was associated with poor survival. We then derived a CINGEC-associated gene expression profile (GEP) signature, CINGECS, using a dataset that has both aCGH and GEP. Genes in CINGECS were mainly involved in DNA damage responses besides in aneuploidy and other generic oncogenic processes contrary to other CIN associated GEP signatures. Finally, we confirmed its survival association in three GEP datasets that encompassed newly diagnosed patients treated with transplant-based protocol with or without novel agents for induction as well as relapsed patients treated with bortezomib. Furthermore, CINGECS was independent of many GEP-based prognostic signatures. In conclusion, our novel CIN measure has definite biological and clinical significance in myeloma.
format	article
author	Tae-Hoon Chung George Mulligan Rafael Fonseca Wee Joo Chng
author_facet	Tae-Hoon Chung George Mulligan Rafael Fonseca Wee Joo Chng
author_sort	Tae-Hoon Chung
title	A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
title_short	A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
title_full	A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
title_fullStr	A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
title_full_unstemmed	A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
title_sort	novel measure of chromosome instability can account for prognostic difference in multiple myeloma.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f85a0564af5e41f999abd3cb5d8d4469
work_keys_str_mv	AT taehoonchung anovelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT georgemulligan anovelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT rafaelfonseca anovelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT weejoochng anovelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT taehoonchung novelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT georgemulligan novelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT rafaelfonseca novelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma AT weejoochng novelmeasureofchromosomeinstabilitycanaccountforprognosticdifferenceinmultiplemyeloma
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A novel measure of chromosome instability can account for prognostic difference in multiple myeloma.

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